Phagocytosis is associated with a burst of oxidative metabolic changes. These reactive oxygen metabolites are essential for the killing of the ingested bacteria. PMN from patients with chronic granulomatous disease (CGD) ingest bacteria normally, but fail to show the usual stimulation of oxidative metabolism normally associated with phagocytosis. They have impaired killing of catalase-positive bacteria. This bactericidal defect can be corrected if H2O2 is delivered to the appropriate site in sufficient amount. I propose to study the effect of menadione (vitamin K3) on the metabolism and function of normal and CGD PMN. It has been shown that auto-oxidation of reduced menadione produces H2O2 and O2. During phagocytosis, a large portion of the plasma membrane is internalized. We have previously demonstrated that the transport carriers of lysine, adenine and adenosine in PMN and rabbit alveolar macrophages are preserved during phagocytosis, suggesting that the plasma membrane is mosaic in character with geographically separate transport and phagocytic sites. I propose to study the effect of phagocytosis on glucose transport systems in normal PMN, CGD PMN and rabbit alveolar macrophages. Phagocytosis by normal PMN and alveolar macrophages but not CGD PMN is accompanied by a marked stimulation of glucose oxidation via the hexose monophosphate shunt. PMN are equipped with potent oxygen-dependent bactericidal systems. These systems are non-specific; they are highly effective against bacteria, fungi, viruses as well as mammalian cells including neoplastic cells. There is evidence that PMN, while killing other cells, are not self destroyed. I propose to study the defense-mechanism of PMN.